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bioRxiv · 10.1101/2020.03.23.003236

Computation of condition-dependent proteome allocation reveals variability in the macro and micro nutrient requirements for growth

Lloyd, C. J.·Monk, J.·Ebrahim, A.·Yang, L.·Palsson, B.
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Abstract

Sustaining a robust metabolic network requires a balanced and fully functioning proteome. In addition to amino acids, many enzymes require cofactors (coenzymes and engrafted prosthetic groups) to function properly. Extensively validated genome-scale models of metabolism and gene expression (ME-models) have the unique ability to compute an optimal proteome composition underlying a metabolic phenotype, including the provision of all required cofactors. Here we use the ME-model for Escherichia coli K-12 MG1655 to computationally examine how environmental conditions change the proteome and its accompanying cofactor usage. We found that: (1) The cofactor requirements computed by the ME model mostly agree with the standard biomass objective function used in models of metabolism alone (M models); (2) ME-model computations reveal non-intuitive variability in cofactor use under different growth conditions; (3) An analysis of ME-model predicted protein use in aerobic and anaerobic conditions suggests an enrichment in the use of prebiotic amino acids in the proteins used to sustain anaerobic growth (4) The ME-model could describe how limitation in key protein components affect the metabolic state of E. coli. Genome-scale models have thus reached a level of sophistication where they reveal intricate properties of functional proteomes and how they support different E. coli lifestyles.

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Lloyd, C. J., Monk, J., Ebrahim, A., Yang, L., Palsson, B.. 2020-03-23. Computation of condition-dependent proteome allocation reveals variability in the macro and micro nutrient requirements for growth. https://doi.org/10.1101/2020.03.23.003236

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